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April 15, 2025
Recent research suggests that inflammation may play a role in ADHD. Inflammation, marked by elevated proteins and cytokines, affects brain development and structure. Evidence suggests it plays a role in the development of ADHD, making the study of inflammatory markers crucial.
The platelet-to-lymphocyte ratio (PLR) is a cost-effective test for predicting outcomes of chronic inflammation and neuroimmune diseases. Studies show PLR may be an important inflammatory marker in the pathophysiology of ADHD in children.
The Study:
A Chinese study team used the National Health and Nutrition Examination Survey (NHANES) database maintained by the National Center for Health Statistics of the United States to investigate the association between PLR and ADHD in children aged 6–14.
The team identified ADHD through prescriptions of ADHD medications.
After exclusions for missing information, the study encompassed 1,455 children.
The authors adjusted for the following potential confounders: sex, age, race, poverty-to-income ratio, maternal age at childbirth, smoking during pregnancy, asthma, health insurance status, dietary inflammatory index, monocyte count, segmented neutrophil count, eosinophil count, and basophil count.
They also split the PLR results into quartiles, with the first quartile having the lowest readings.
Prescriptions of ADHD medications were twice as frequent among children in the second quartile as they were among children in the first quartile. They were four times as frequent among children in the third quartile than among children in the first quartile.
Conclusion:
The team concluded, “These findings further support the potential role of inflammation in the onset and development of ADHD, providing preliminary evidence for PLR as a potential biomarker for ADHD and suggesting its possible use in identifying high-risk populations. However, considering the limitations of this study, future research should be designed as larger-scale, prospective, multi-center randomized controlled trials to validate these findings and further explore the relationship between inflammatory mechanisms and ADHD.”
In other words, this study suggests that while high PLR values may serve as a potential biomarker for ADHD, particularly in specific high-risk groups, further research is needed to confirm these findings and fully understand the role of inflammation in ADHD development. Larger, more robust studies will be crucial to validating PLR as a reliable tool for identifying at-risk populations.
Xianhua Li, Yan Luo, Xiaodan Zeng, Xuewen Qiu, Yang Hua, and Lingling Zhan, “Correlation analysis of the platelet-to-lymphocyte ratio with attention-deficit hyperactivity disorder in children aged 6–14: based on the National Health and Nutrition Examination Survey database,” CNS Spectrums (2025), 30(1), e20, 1–9, https://doi.org/10.1017/S1092852924002475.
Background:
Sleep is more than simple rest. When discussing sleep, we tend to focus on the quantity rather than the quality, how many hours of sleep we get versus the quality or depth of sleep. Duration is an important part of the picture, but understanding the stages of sleep and how certain mental health disorders affect those stages is a crucial part of the discussion.
Sleep is an active mental process where the brain goes through distinct phases of complex electrical rhythms. These phases can be broken down into non-rapid eye movement (NREM) and rapid eye movement (REM). The non-rapid eye movement phase consists of three stages of the four stages of sleep, referred to as N1, N2(light sleep), and N3(deep sleep). N4 is the REM phase, during which time vivid dreaming typically occurs.
Two of the most important measurable brain rhythms occur during non-rapid eye movement (NREM) sleep. These electrical rhythms are referred to as slow waves and sleep spindles. Slow waves reflect deep, restorative sleep, while spindles are brief bursts of brain activity that support memory and learning.
The Study:
A new research review has compiled data on how these sleep oscillations differ across psychiatric conditions. The findings suggest that subtle changes in nightly brain rhythms may hold important clues about a range of disorders, from ADHD to schizophrenia.
The Results:
People with ADHD showed increased slow-spindle activity, meaning those brief bursts of NREM activity were more frequent or stronger than in people without ADHD. Why this happens isn’t fully understood, but it may reflect differences in how the ADHD brain organizes information during sleep. Evidence for slow-wave abnormalities was mixed, suggesting that deep sleep disruption is not a consistent hallmark of ADHD.
Among individuals with autism spectrum disorder (ASD), results were less consistent. However, some studies pointed to lower “spindle chirp” (the subtle shift in spindle frequency over time) and reduced slow-wave amplitude. Lower amplitude suggests that the brain’s deep-sleep signals may be weaker or less synchronized. Researchers are still working to understand how these patterns relate to sensory processing, learning differences, or daytime behavior.
People with depression tended to show reduced slow-wave activity and fewer or weaker sleep spindles, but this pattern appeared most strongly in patients taking antidepressant medications. Since antidepressants can influence sleep architecture, researchers are careful not to overinterpret the changes. Nevertheless, these changes raise interesting questions about how both depression and its treatments shape the sleeping brain.
In post-traumatic stress disorder (PTSD), the trend moved in the opposite direction. Patients showed higher spindle frequency and activity, and these changes were linked to symptom severity which suggests that the brain may be “overactive” during sleep in ways that relate to hyperarousal or intrusive memories. This strengthens the idea that sleep physiology plays a role in how traumatic memories are processed.
The clearest and most reliable findings emerged in psychotic disorders, including schizophrenia. Across multiple studies, individuals showed: Lower spindle density (fewer spindles overall), reduced spindle amplitude and duration, correlations with symptom severity, and cognitive deficits.
Lower slow-wave activity also appeared, especially in the early phases of illness. These results echo earlier research suggesting that sleep spindles, which are generated by thalamocortical circuits, might offer a window into the neural disruptions that underlie psychosis.
The Take-Away:
The review concludes with a key message: While sleep disturbances are clearly present across psychiatric conditions, the field needs larger, better-standardized, and more longitudinal studies. With more consistent methods and longer follow-ups, researchers may be able to determine whether these oscillations can serve as reliable biomarkers or future treatment targets.
For now, the take-home message is that the effects of these mental health disorders on sleep are real and measurable.
Many studies have shown that ADHD is associated with increased risks of suicidal behavior, substance misuse, injuries, and criminality. As we often discuss in our blogs, treatments for ADHD include medication and non-medication options, such as CBT (Cognitive Behavioral Therapy). While non-drug approaches are often used for young children or mild cases of ADHD, medications – both stimulants and non-stimulants – are common for adolescents and adults.
Global prescriptions for ADHD drugs have risen significantly in recent years, raising questions about their safety and effectiveness. Randomized controlled trials have demonstrated that medication can help reduce the core symptoms of ADHD. However, research from these trials still offers limited or inconclusive insights into wider and more significant clinical outcomes, such as suicidal behavior and substance use disorder.
An international study team conducted a nationwide population study using the Swedish national registers. Sweden has a single-payer national health insurance system, which covers nearly every resident, enabling such studies. The researchers examined all Swedish residents aged 6 to 64 who received their first ADHD diagnosis between 2007 and 2018. Analyses of criminal behavior and transport accidents focused on a subgroup aged 15 to 64, since individuals in Sweden must be at least 15 years old to be legally accountable for crimes or to drive.
The team controlled for confounding factors, including demographics (age at ADHD diagnosis, calendar year, sex, country of birth, highest education (using parental education for those under 25), psychiatric and physical diagnoses, dispensations of psychotropic drugs, and health care use (outpatient visits and hospital admissions for both psychiatric and non-psychiatric reasons).
Time-varying covariates from the previous month covered diagnoses, medication dispensations, and healthcare use. During the study, ADHD treatments licensed in Sweden included amphetamine, atomoxetine, dexamphetamine, guanfacine, lisdexamphetamine, and methylphenidate.
After accounting for covariates, individuals diagnosed with ADHD who received medication treatment showed better outcomes than those who did not. Specifically:
-Suicidal behaviors dropped by roughly 15% in both first-time and recurrent cases.
-Initial criminal activity decreased by 13%, with repeated offences falling by 25%.
-Substance abuse initiation declined by 15%, while recurring substance abuse was reduced
by 25%.
-First automotive crashes were down 12%, and subsequent crashes fell by 16%.
There was no notable reduction in first-time accidental injuries, and only a marginally significant 4% decrease in repeated injuries.
The team concluded, “Drug treatment for ADHD was associated with beneficial effects in reducing the risks of suicidal behaviours, substance misuse, transport accidents, and criminality, but not accidental injuries when considering first event rate. The risk reductions were more pronounced for recurrent events, with reduced rates for all five outcomes.”
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Background:
Pharmacotherapies, such as methylphenidate, are highly effective for short-term ADHD management, but issues remain with medication tolerability and adherence. Some patients experience unwanted side effects from stimulant medications, leaving them searching for alternative ADHD treatments. Alternative treatments such as cognitive training, behavioral therapies, psychological interventions, neurofeedback, and dietary changes have, so far, shown limited success. Thus, there is a critical need for non-pharmacological options that boost neurocognitive performance and address core ADHD symptoms.
First— What Are NIBS (Non-Invasive Brain Stimulation) Techniques?
Non-invasive brain stimulation (NIBS) techniques, including transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS), transcranial alternating current stimulation (tACS), and repetitive transcranial magnetic stimulation (rTMS) are generating growing attention within the scientific community.
NIBS techniques are methods that use external stimulation, such as magnets or electrical currents, to affect brain activity without any invasive procedures. In transcranial alternating current stimulation (tACS), for example, small electrodes are placed on the scalp of the patient, and a weak electrical current is administered.
The theory behind these techniques is that when a direct current is applied between two or more electrodes placed on specific areas of the head, it makes certain neurons more or less likely to fire. This technique has been successfully used to treat conditions like depression and anxiety, and to aid recovery from stroke or brain injury.
The Study:
Previous meta-analyses have produced conflicting indications of efficacy. A Chinese research team consisting of sports and rehabilitative medicine professionals has just published a network meta-analysis to explore this further, through direct comparison of five critical outcome domains: inhibitory control, working memory, cognitive flexibility, inattention, hyperactivity and impulsivity.
To be included, randomized controlled trials needed to have participants diagnosed with ADHD, use sham control groups, and assess ADHD symptoms and executive functions – such as inhibitory control, working memory, cognitive flexibility, inattention, hyperactivity, and impulsivity – using standardized tests.
A total of thirty-seven studies encompassing 1,615 participants satisfied the inclusion criteria. It is worth noting, however, that the authors did not specify the number of randomized controlled trials nor the number of participants included in each arm of the network meta-analysis.
Furthermore, the team stated, “We checked for potential small study effects and publication bias by conducting comparison-adjusted funnel plots,” but did not share their findings. They also did not provide information on outcome variation (heterogeneity) among the RCTs.
Results:
Ultimately, none of the interventions produced significant improvements in ADHD symptoms, whether in inattention symptoms or hyperactivity/impulsivity symptoms. Likewise, none of the interventions produced significant improvements in inhibitory control. Some tDCS interventions enhanced working memory and cognitive flexibility, but details about trial numbers and participants were missing. The team concluded, “none of the NIBS interventions significantly improved inhibitory control compared to sham controls. … In terms of working memory, anodal tDCS over the left DLPFC plus cathodal tDCS over the right DLPFC … and anodal tDCS over the right inferior frontal cortex (rIFC) plus cathodal tDCS over the right supraorbital area ... were associated with significant improvements compared to sham stimulation. For cognitive flexibility, only anodal tDCS over the left DLPFC plus cathodal tDCS over the right supraorbital area demonstrated a statistically significant benefit relative to sham. ... Compared to the sham controls, none of the NIBS interventions significantly improved inattention. ... Compared to the sham controls, none of the NIBS interventions significantly improved hyperactivity and impulsivity.”
How Should We Interpret These Results?
In a word, skeptically.
If one were to read just the study’s abstract, which states, “The dual-tDCS and a-tDCS may be considered among the preferred NIBS interventions for improving cognitive function in ADHD”, it might seem that the takeaway from this study is that this combination of brain stimulation techniques might be a viable treatment option for those with ADHD. Upon closer inspection, however, the results do not suggest that any of these methods significantly improve ADHD symptoms. Additionally, this study suffers from quite a few methodological flaws, so any results should be viewed critically.
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